NSAIDs and Acute Renal Failure Flashcards
Drug elimination in the kidneys is normally impaired in the elderly due to what 2 things
reduced renal blood flow
decreased GFR
Dosage adjustment according to renal function is indicated for many drugs in order to avoid what 3 things
accumulation of drugs/metabolites
adverse reactions
aggravation of renal impairment
Renal dysfunction alters renal excretion of drug/metabolites and also leads to modification in what 3 things of drug substances?
distribution
transport
biotransformation
What are the 3 processes that can potentially contribute to the renal clearance of a drug?
glomerular filtration
tubular secretion
tubular reabsorption
perfusion rate limited
the extraction ratio is not limited to the unbound fraction of the drug
capacity rate limited
the extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in red blood cells
The tubular reabsorption of drugs is considered a ____________ process for the majority of drugs and drug metabolites
passive
What is the driving force that powers the tubular reabsorption of drugs?
the extensive reabsorption of filtered water long the tubule
Name the peptide transporters that are expressed on the apical membrane of renal epithelial cells that mediate the tubular reabsorption of peptide-like drugs like beta lactam and ACE inhibitors
PEPT1, PEPT2
GFR of normal renal function
> 80
GFR mild renal impairment
50-80
GFR moderate renal impairment
30-50
GFR severe renal impairment
<30
GFR of end-stage renal disease
REQUIRES DIALYSIS
NSAIDs are used by what percentage of people over 65 every day?
20-30%
What are 4 reasons adults are at a higher risk for experiencing adverse effects of NSAIDs
higher use
increased prevalence of conditions exacerbated by NSAIDs (HTN, CHF, Renal insuff.)
larger numbers of comorbid conditions
higher use of other meds
______________ declines with age irrespective of the use of drug therapy
RENAL FUNCTION
__________________locally modulate the effects of both systemic and locally produced vaso-constrictor hormones
eicosanoids
what ar ethe 2 predominant mediators of physiologic activity in the kidney
PGI2, PGE2
what do PGI2 and PGE2 do in the kidney?
induce vasodilation of interlobular arteries, affarent and efferent arterioles and glomeruli
why is risk of NSAID-associated acute renal failure in healthy people negligible
because the basal PG production is low in healthy people
what are some risk factors that render the kidney prostaglandin dependent and so place pts at risk of ARF when they take NSAIDs
true intravascular volume depletion vomiting diarrhea diuretics effective intravascular volume depletion congestive heart failure cirrhosis kidney disease ARF CKD meds ACE inhibitors ARBs old age
How do PGI2 and PGE2 preserve GFR
by antagonizing arteriolar vasoconstriction and blunting mesangial and podocyte contraction induced by endogenous vasopressors
the risks of lowering GFR in pts with underlying pathologic states increases with the _____________- and the _________________ of NSAID consumption
dose, duration
